In all vertebrate species studied, the main central population of GnRH neurones, which produces the final messages regulating reproduction, originates outside the brain. Early during fetal life, they appear in the olfactory placode epithelium and then migrate toward the base of the telencephalon in close association with the nervus terminalis, penetrate the brain within the nervus terminalis roots, reach their final locations and eventually grow axons toward their targets. Only part of this process is documented in ruminants. In the sheep fetus, the olfactory placode develops between day 22 and day 26 of gestation, but the first GnRHimmunoreactive neurones have been detected only at day 35, associated with the extracerebral part of the nervus terminalis. During the next 30 -40 days, the GnRH neuronal systems progressively invade the brain. In both sexes, most of the development, in terms of distribution and morphology of the neurones, appears to be completed by the middle of gestation (term being on day 145). On day 85 GnRH-immunoreactive neuronal systems of male and female fetuses have also been reported to be very similar to GnRH neuronal systems of adult females. Attention should now be focused on the earliest developmental steps.

Objectives Several serological SARS-CoV-2 immunoassays have been developed recently but require external validation before widespread use. This study aims at assessing the analytical and clinical performance of the iFlash® anti-SARS-CoV-2 chemiluminescence assay for the detection of both IgM and IgG antibodies. The kinetics of the antibody response was also evaluated. Design & Methods The precision, carry-over, linearity, limit of blank, detection and quantification were assessed. Sensitivity analysis was performed by using 178 sera collected from 154 RT-PCR confirmed COVID-19 patients. The specificity analysis was performed from 75 selected non-SARS-CoV-2 sera with a potential cross-reaction to the SARS-CoV-2 immunoassay. Results This iFlash® SARS-CoV-2 assay showed excellent analytical performance. After 2 weeks since symptom onset, the sensitivities for IgM and IgG were 62.2% (95% CI: 52.3–71.2%) and 92.9%% (95% CI: 85.7–96.7%), respectively by using the cut-off provided by the manufacturer. After cut-off optimization (i.e. >2.81 for IgM and >4.86 for IgG), the sensitivity for IgM and IgG were 81.6 (95% CI: 72.7–88.1%) and 95.9% (95% CI: 89.4–98.7%), respectively. Optimized cut-off for IgG improved the sensitivity to reach 100% (95%CI: 87.6–100) from 28 days since symptom onset. Conclusions This study shows that the iFlash® SARS-CoV-2 assay from YHLO biotechnology, has satisfactory analytical performance. Nevertheless, the sensitivity of the IgM is limited for a proper clinical use compared to IgG. The determination of anti-SARS-CoV-2 IgG antibodies from 28 days since symptom onset was associated with high sensitivity, especially using optimized cut-offs (i.e. 100%).

In the general diabetic adolescent population, the efficacy of a three-injection regimen is somewhat superior to that of a conventional two-injection regimen, particularly in patients previously poorly controlled. The acceptability of this regimen being excellent, its increased use should be considered in this age-group.

Background Evaluation of an individual’s thrombin‐generating capacity enables a global assessment of the coagulation cascade and is therefore thought to better reflect the clotting function of blood. However, the lack of standardization still hampers the use in routine clinical practice. Methods Nineteen healthy subjects were sampled once a week for 5 consecutive weeks. Thrombin generation assay (TGA) was performed in duplicate by calibrated automated thrombogram (CAT) on platelet poor plasma with and without thrombomodulin. After exclusion of outliers, a nested analysis of variance (ANOVA) was performed to evaluate the biological variability (BV) results. Analytical variation (CVA), within‐individual variation (CVI), between‐individual variation (CVG), index of individuality (II), and reference change value (RCV) were calculated. Results All parameters taken together, the CVA, CVI, and CVG without TM, ranged from 2.8% to 6.5%, from 4.1% to 13.3% and from 10.4% to 28.4%, respectively. For TG with TM, CVI and CVG were higher and ranged from 5.0% to 18.1% and from 14.9% to 35.3%, respectively. For endogenous thrombin potential (ETP), a CVI of 4.1% and CVG of 10.4% were obtained without addition of thrombomodulin (TM). With addition of TM, both CVI and CVG were higher: 14.0% and 34.8%, respectively. The II was low and the RCV ranged from 17.2% to 50.4%. Conclusion CAT parameters are highly individualized and population‐based reference values could be called into question. The assessment of BV and RCV for thrombin generation assays could optimize interpretation of serial patient results and guide setting of analytical specification goals.

Background Interpretation of thyroid function tests by means of biological variation (BV) data is essential to identify significant changes between serial measurements at an individual level. Data on thyroid parameters in adults are limited. Objectives We aimed at determining the BV of four thyroid function test (thyroid‐stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3) and thyroglobulin (Tg)) by applying recent recommendations to acquire BV data on a latest generation of immunoassay. Methods Nineteen healthy volunteers (8 males and 11 females) were drawn every week during 5 consecutive weeks. Samples were analysed in duplicate on the Cobas 602 analyzer (Roche Diagnostics). After normality assessment, outlier exclusion and homogeneity of variance analysis, analytical variation (CVA), within‐subject biological variation (CVI) and between‐subject biological variation (CVG) were determined using nested ANOVA. Results CVA, CVI and CVG were 0.9%, 19.7% and 37.6% for TSH; 3.6%, 4.6% and 10.8% for FT4; 2.2%, 6.0% and 8.6% for FT3; and 0.9%, 15.4% and 84.9% for Tg. Index of individuality (II) for all parameters was between 0.2 and 0.7. The percentage above which the change between two measures is truly significant (reference change value) was 54.7% for TSH, 16.2% for FT4, 17.7% for FT3 and 42.8% for Tg. Conclusion Based on recent international recommendations, our study provides updated BV data for four thyroid function tests in European healthy volunteers. Reliable BV characteristics, and especially RCV, can facilitate the interpretation of consecutive thyroid function tests in an individual and therefore have the potential to efficiently support clinical decisions regarding thyroid diseases.